当前位置： SCI文献检索 > NEUROSCIENCE期刊下所有文献 > Alteration of activator protein 1 DNA binding activity in gentamicin-induced hair cell degeneration.

Alteration of activator protein 1 DNA binding activity in gentamicin-induced hair cell degeneration.

Abstract：

:Sensorineural hearing loss is often associated with damage of cochlear hair cells and/or of the neurons of the auditory pathway. This damage can result from a variety of causes, e.g. genetic disorders, aging, exposure to certain drugs such as aminoglycosides, infectious disease and intense sound overexposure. Intracellular events that mediate aspects of aminoglycoside-mediated damage to hair cells have been partially unraveled. Several independent research groups have demonstrated a crucial role of mitogen-activated protein kinase signaling in aminoglycoside-induced ototoxicity. Mitogen-activated protein kinases are important mediators of signal transduction from the cell surface to the nucleus. Jun N-terminal kinases, members of the mitogen-activated protein kinase family, are strongly activated in cell culture conditions by stress inducing stimuli, including ultraviolet light, heat shock and tumor necrosis factor; therefore they are also referred to as stress-activated protein kinases. In hair cells aminoglycoside treatment was shown to activate the Jun N-terminal kinase signaling pathway. Activation of Jun N-terminal kinase leads to phosphorylation and thereby activation of transcription factors and consequently to altered gene expression. There are many nuclear Jun N-terminal kinase substrates including c-Jun, ATF-2, and Elk-1 proteins. One of the downstream targets of Jun N-terminal kinase is the transcription factor activating protein-1. Activating protein-1 is a dimeric complex composed of members of the Fos and Jun proteins. A variety of different stimuli is known to induce activating protein-1 activity. Induction of activating protein-1 is thought to play a central role in reprogramming gene expression in response to external stimuli. In this study we have analyzed the effect of gentamicin treatment on the downstream targets of Jun N-terminal kinase. Our results demonstrate that gentamicin treatment of explants of organ of Corti results in increased activating protein-1 binding activity. The main component of these activating protein-1 complexes is the c-Fos protein. Moreover, we show that the activating protein-1 induction is transient and occurs exclusively in hair cells of rat organ of Corti explants.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Albinger-Hegyi A,Hegyi I,Nagy I,Bodmer M,Schmid S,Bodmer D

doi

10.1016/j.neuroscience.2005.10.010

keywords:

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

971-80

issue

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(05)01119-X

journal_volume

137

pub_type

杂志文章

在线工具

Alteration of activator protein 1 DNA binding activity in gentamicin-induced hair cell degeneration.